Arginine is a conditionally nonessential amino acid, meaning that most of the time it can be manufactured by the human body, and does not need to be obtained directly through the diet. The biosynthetic pathway, however, does not produce sufficient arginine, and some must still be consumed. Individuals with poor nutrition or certain physical conditions may need to increase their intake of foods containing arginine or take arginine supplements.
Arginine is synthesized from citrulline by the sequential action of the cytosolic enzymes argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL). In terms of energy, this is costly, as the synthesis of each molecule of argininosuccinate requires hydrolysis of adenosine triphosphate (ATP) to adenosine monophosphate (AMP), i.e., two ATP equivalents. In essence, taking an excess of arginine gives more energy by saving ATPs that can be used elsewhere.
Citrulline can be derived from multiple sources:                from arginine via nitric oxide synthase (NOS)        from ornithine via catabolism of proline or glutamine/glutamate        from asymmetric dimethylarginine (ADMA) via DDAH        
On a whole-body basis, synthesis of arginine occurs principally via the intestinal-renal axis, wherein epithelial cells of the small intestine, which produce citrulline primarily from glutamine and glutamate, collaborate with the proximal tubule cells of the kidney, which extract citrulline from the circulation and convert it to arginine, which is returned to the circulation. As a consequence, impairment of small bowel or renal function can reduce endogenous arginine synthesis, thereby increasing the dietary requirement.
Synthesis of arginine from citrulline also occurs at a low level in many other cells, and cellular capacity for arginine synthesis can be markedly increased under circumstances that also induce iNOS. Thus, citrulline, a co-product of the NOS-catalyzed reaction, can be recycled to arginine in a pathway known as the citrulline-NO or arginine-citrulline pathway. This is demonstrated by the fact that, in many cell types, citrulline can substitute for arginine to some degree in supporting NO synthesis. However, recycling is not quantitative because citrulline accumulates along with nitrate and nitrite, the stable end-products of NO, in NO-producing cells.
Arginine plays an important role in cell division, the healing of wounds, removing ammonia from the body, immune function, and the release of hormones.
The roles of arginine include:                Precursor for the synthesis of nitric oxide (NO). Non-L-arginine derived NO can be generated by the nitrate-nitrite-nitric oxide pathway that is monitored through saliva testing.        Reduces healing time of injuries (particularly bone).        Quickens repair time of damaged tissue.        Helps decrease blood pressure in clinical hypertensive subjects. NO-mediated decrease in blood pressure is influenced by both the L-arginine-dependent nitric oxide synthase pathway and non-L-arginine or alternative pathway through nitrate-rich foods such as beets and spinach.        
Arginine is the immediate precursor of nitric oxide (NO), urea, ornithine, and agmatine; is necessary for the synthesis of creatine; and can also be used for the synthesis of polyamines (mainly through ornithine and to a lesser degree through agmatine), citrulline, and glutamate. As a precursor of nitric oxide, arginine may have a role in the treatment of some conditions where vasodilation is required. The presence of asymmetric dimethylarginine (ADMA), a close relative, inhibits the nitric oxide reaction; therefore, ADMA is considered a marker for vascular disease, just as L-arginine is considered a sign of a healthy endothelium.
Intravenously-administered arginine stimulates the secretion of growth hormone, and is used in growth hormone stimulation tests. Two studies have found that oral arginine supplementation is also effective at increasing resting GH levels. The first study found that oral preparations of arginine are effective at increasing growth hormone levels. In fact, the 9-gram dose resulted in mean peak GH levels of 6.4 (+/−1.3) μg/L versus placebo levels of 2.9 (+/−0.7). Another study found similar results. It included resting versus exercise and oral L-arginine versus oral placebo. The authors concluded that “Oral arginine alone (7 g) stimulated GH release, but a greater GH response was seen with exercise alone. The combined effect of arginine before exercise attenuates the GH response . . . GH production: Ex>Arg+Ex>Arg>placebo” suggesting against supplementing with arginine alone prior to exercise if the goal is to raise GH levels, but concurring with the previous study that oral L-arginine increases GH on days free of significant exercise.
In contrast to these two studies that found increased resting GH due to oral arginine supplementation, a third study did not find increase in resting GH levels from oral supplementation. In that study, oral preparations of L-arginine were ineffective at increasing growth hormone levels despite being effective at increasing plasma levels of L-arginine. However, bioavailability data was not available, and it is possible that quality, stability and/or uptake was a problem.
Intravenous infusion of arginine reduces blood pressure in patients with hypertension as well as normal subjects. A meta-analysis showed that L-arginine reduces blood pressure with pooled estimates of 5.4/2.7 mmHg for SBP/DBP. Supplementation with L-arginine reduces diastolic blood pressure and lengthens pregnancy for women with gestational hypertension, including women with high blood pressure as part of pre-eclampsia. It does not, however, lower systolic blood pressure or improve the baby's weight at birth.
Carnitine is another important biological molecule. It is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. Carnitine exists in two stereoisomers: its biologically active form is L-carnitine, whereas its enantiomer, D-carnitine, is biologically inactive.
In eukaryotic cells, carnitine is required for the transport of fatty acids from the intermembraneous space in the mitochondria, into the mitochondrial matrix during the breakdown of lipids (fats) for the generation of metabolic energy, and is widely available as a nutritional supplement. Carnitine was originally found as a growth factor for mealworms and labeled vitamin BT, although carnitine is not a proper vitamin.
Carnitine transports long-chain acyl groups from fatty acids into the mitochondrial matrix, so they can be broken down through β-oxidation to acetyl CoA to obtain usable energy via the citric acid cycle. Fatty acids must be activated before binding to the carnitine molecule to form ‘acylcarnitine’. The free fatty acid in the cytosol is attached with a thioester bond to coenzyme A (CoA). This reaction is catalyzed by the enzyme fatty acyl-CoA synthetase and driven to completion by inorganic pyrophosphatase.
The acyl group on CoA can now be transferred to carnitine and the resulting acylcarnitine transported into the mitochondrial matrix. This occurs via a series of similar steps:                Acyl CoA is transferred to the hydroxyl group of carnitine by carnitine acyltransferase I (palmitoyltransferase) located on the outer mitochondrial membrane.        Acylcarnitine is shuttled inside by a carnitine-acylcarnitine translocase.        Acylcarnitine is converted to acyl CoA by carnitine acyltransferase II (palmitoyltransferase) located on the inner mitochondrial membrane. The liberated carnitine returns to the cytosol.        
Human genetic disorders, such as primary carnitine deficiency, carnitine palmitoyltransferase I deficiency, carnitine palmitoyltransferase II deficiency and carnitine-acylcarnitine translocase deficiency, affect different steps of this process.
Carnitine acyltransferase I and peroxisomal carnitine octanoyl transferase (CROT) undergo allosteric inhibition as a result of malonyl-CoA, an intermediate in fatty acid biosynthesis, to prevent futile cycling between β-oxidation and fatty acid synthesis.
There may be a link between dietary consumption of carnitine and atherosclerosis, but there is also evidence that it lowers the risk of mortality and arrythmias after an acute myocardial infarction.
When certain species of intestinal bacteria were exposed to carnitine from food, they produced a waste product, trimethylamine, which is transformed in the liver to trimethylamine N-oxide (TMAO). TMAO may be associated with atherosclerosis. The presence of large amounts of TMAO-producing bacteria was a consequence of a long-term diet rich in meat. However, when the authors compared the risk of cardiovascular events to the levels of carnitine and TMAO, they found that the risk was higher in those with higher TMAO levels, independent of the carnitine levels.
Vegetarian and vegans who ate a single meal of meat had much lower levels of TMAO in their bloodstream than did regular meat-eaters, as vegetarian and vegans had lower levels of the intestinal bacteria that converts carnitine into TMAO.
Another study has found evidence of a second path for atherogenic activity of carnitine, passing through a different metabolite: γ-butyrobetaine (γBB)
In the course of human aging, carnitine concentration in cells diminishes, affecting fatty acid metabolism in various tissues. Particularly adversely affected are bones, which require continuous reconstructive and metabolic functions of osteoblasts for maintenance of bone mass. A 2008 study found that supplementing with L-carnitine decreased bone turnover and increased bone mineral density in rats.
A 2004 study found that L-carnitine acts as a peripheral antagonist of thyroid hormone action. In particular, L-carnitine inhibits both triiodothyronine (T3) and thyroxine (T4) entry into the cell nuclei. For this reason, L-carnitine has been proposed as a supplement to treat hyperthyroidism. A 2001 study found that L-carnitine was useful in both reversing and preventing hyperthyroid symptoms.
Carnitine has been proposed as a supplement to treat a variety of health conditions including heart attack, heart failure, angina, narcolepsy, and diabetic neuropathy, but not fatigue, improving exercise performance, nor wasting syndrome (weight loss). There is also some suggestion that use of acetyl-carnitine and L-arginine may improve sperm motility in men with sperm abnormalities.
Dehydroepiandrosterone/dehydroepiandrostenedione (DHEA, more correctly didehydroepiandrosterone), also known as androstenolone or prasterone (INN), as well as 3β-hydroxyandrost-5-en-17-one or 5-androsten-3β-ol-17-one, is an important endogenous steroid hormone. It is the most abundant circulating steroid hormone in humans, in whom it is produced in the adrenal glands, the gonads, and the brain, where it functions predominantly as a metabolic intermediate in the biosynthesis of the androgen and estrogen sex steroids. However, DHEA also has a variety of potential biological effects in its own right, binding to an array of nuclear and cell surface receptors, and acting as a neurosteroid.
Zinc and magnesium are also essential elements in the human body. Zinc is an essential trace element for humans, is found in hundreds of enzymes, serves as structural ions in transcription factors and is stored and transferred in metallothioneins. It is typically the second most abundant transition metal in organisms after iron and it is the only metal which appears in all enzyme classes.
There are 2-4 grams of zinc distributed throughout the human body. Most zinc is in the brain, muscle, bones, kidney, and liver, with the highest concentrations in the prostate and parts of the eye. Semen is particularly rich in zinc, which is a key factor in prostate gland function and reproductive organ growth.
In humans, zinc interacts with a wide range of organic ligands, and has roles in the metabolism of RNA and DNA, signal transduction, and gene expression. It also regulates apoptosis. A 2006 study estimated that about 10% of human proteins (2800) potentially bind zinc, in addition to hundreds which transport and traffic zinc; a similar in silico study in the plant Arabidopsis thaliana found 2367 zinc-related proteins.
In the brain, zinc is stored in specific synaptic vesicles by glutamatergic neurons and can modulate brain excitability. It plays a key role in synaptic plasticity and so in learning. However, it has been called “the brain's dark horse” because it also can be a neurotoxin, suggesting zinc homeostasis plays a critical role in normal functioning of the brain and central nervous system.
Because of the important interaction between phosphate and magnesium ions, magnesium ions are essential to the basic nucleic acid chemistry of life, and thus are essential to all cells of all known living organisms. Over 300 enzymes require the presence of magnesium ions for their catalytic action, including all enzymes utilizing or synthesizing ATP, or those that use other nucleotides to synthesize DNA and RNA. ATP exists in cells normally as a chelate of ATP and a magnesium ion.
Magnesium deficiency (hypomagnesemia) is common and vastly under reported: it is found in 2.5-15% of the general population but may be much higher due to the body's attempt to keep blood magnesium levels relatively stable by releasing magnesium from bone and tissues. So, even though the blood level may be normal, the body may actually be deficient. The primary cause of deficiency is decreased dietary intake: only 32% of people in the United States meet the recommended daily allowance. Other causes are increased renal or gastrointestinal loss, an increased intracellular shift, and proton-pump inhibitor antacid therapy. Most are asymptomatic, but symptoms referable to neuromuscular, cardiovascular, and metabolic dysfunction may occur. Alcoholism is often associated with magnesium deficiency. Chronically low serum magnesium levels are associated with metabolic syndrome, diabetes mellitus type 2 and hypertension.
Not surprisingly, the patent literature is replete with medical uses for these molecules and trace elements, or uses as nutritional support uses for certain disease states. However, there is always room for improved formulations designed to treat specific conditions.